BACKGROUND Impaired interstitial cells of Cajal(ICCs)are central to the pathophysiology of acute cholecystitis(AC).Common bile duct ligation is a common model of AC,producing acute inflammatory changes and decrease in...BACKGROUND Impaired interstitial cells of Cajal(ICCs)are central to the pathophysiology of acute cholecystitis(AC).Common bile duct ligation is a common model of AC,producing acute inflammatory changes and decrease in gallbladder contractility.AIM To investigate the origin of slow wave(SW)in the gallbladder and the effect of ICCs on gallbladder contractions during the process of AC.METHODS Methylene blue(MB)with light was used to establish selective impaired ICCs gallbladder tissue.Gallbladder motility was assessed using the frequency of SW and gallbladder muscle contractility in vitro in normal control(NC),AC12h,AC24h,and AC48h groups of guinea pigs.Hematoxylin and eosin and Massonstained gallbladder tissues were scored for inflammatory changes.ICCs pathological changes alterations were estimated using immunohistochemistry and transmission electron microscopy.The alterations of c-Kit,α-SMA,cholecystokinin A receptor(CCKAR),and connexin 43(CX43)were assessed using Western blot.RESULTS Impaired ICCs muscle strips resulted in the decrease in gallbladder SW frequency and contractility.The frequency of SW and gallbladder contractility were significantly lower in the AC12h group.Compared with the NC group,the density and ultrastructure of ICCs were remarkably impaired in the AC groups,especially in the AC12h group.The protein expression levels of c-Kit were significantly decreased in the AC12h group,while CCKAR and CX43 protein expression levels were significantly decreased in the AC48h group.CONCLUSION Loss ICCs could lead to a decrease in gallbladder SW frequency and contractility.The density and ultrastructure of ICCs were clearly impaired in the early stage of AC,while CCKAR and CX43 were significantly reduced at end stage.展开更多
BACKGROUND The lack of effective pharmacotherapies for nonalcoholic fatty liver disease(NAFLD)is mainly attributed to insufficient research on its pathogenesis.The pathogenesis of TM6SF2-efficient NAFLD remains unclea...BACKGROUND The lack of effective pharmacotherapies for nonalcoholic fatty liver disease(NAFLD)is mainly attributed to insufficient research on its pathogenesis.The pathogenesis of TM6SF2-efficient NAFLD remains unclear,resulting in a lack of therapeutic strategies for TM6SF2-deficient patients.AIM To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency.METHODS Liver samples collected from both NAFLD mouse models and human participants(80 cases)were used to evaluate the expression of TM6SF2 by using western blotting,immunohistochemistry,and quantitative polymerase chain reaction.RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2.Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD.MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency.RESULTS Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models.TM6SF2 overexpression can reduce hepatic lipid accumulation,suggesting a protective role for TM6SF2 in a high-fat diet(HFD).Downregulation of TM6SF2,simulating the TM6SF2 E167K mutation condition,increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis,accompanied by impaired fatty acid oxidation.Owing to the potential effect of TM6SF2 deficiency on lipid metabolism,the application of an acetyl-CoA carboxylase inhibitor(MK-4074)could reverse the NAFLD phenotypes caused by TM6SF2 deficiency.CONCLUSION TM6SF2 plays a protective role in the HFD condition;its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism,and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.展开更多
BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface barrier.Notably,these enzymes p...BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface barrier.Notably,these enzymes play a significant role in the development of diverse tumors.AIM To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma(CCA).METHODS We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression Omnibus.The study identified differentially expressed genes between tumor tissues and adjacent normal tissues,with a focus on PLA2G2A and PLA2G12B.Gene Set Enrichment Analysis was utilized to pinpoint associated pathways.Moreover,relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted,and their correlation with the prognosis of CCA was evaluated.RESULTS PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA,manifesting significant variations in expression levels in urine and serum between CCA patients and healthy individuals.Elevated expression of PLA2G2A was correlated with poorer overall survival in CCA patients.Additionally,the study delineated pathways and miRNAs associated with these genes.CONCLUSION Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for CCA.The increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA,and their expression levels are indicative of prognosis,underscoring their potential utility in clinical settings.展开更多
The physiological function of the gastrointestinal(GI)tract is based on the slow wave generated and transmitted by the interstitial cells of Cajal.Extracellular myoelectric recording techniques are often used to recor...The physiological function of the gastrointestinal(GI)tract is based on the slow wave generated and transmitted by the interstitial cells of Cajal.Extracellular myoelectric recording techniques are often used to record the characteristics and propagation of slow wave and analyze the models of slow wave transmission under physiological and pathological conditions to further explore the mechanism of GI dysfunction.This article reviews the application and research progress of electromyography,bioelectromagnetic technology,and high-resolution mapping in animal and clinical experiments,summarizes the clinical application of GI electrical stimulation therapy,and reviews the electrophysiological research in the biliary system.展开更多
基金Supported by the Pudong New Area Clinical Traditional Chinese Medicine of Top Discipline Project,No.PDZY-2018-0603 and the Featured Clinical Discipline Project of Shanghai Pudong,No.PWYts2021-06.
文摘BACKGROUND Impaired interstitial cells of Cajal(ICCs)are central to the pathophysiology of acute cholecystitis(AC).Common bile duct ligation is a common model of AC,producing acute inflammatory changes and decrease in gallbladder contractility.AIM To investigate the origin of slow wave(SW)in the gallbladder and the effect of ICCs on gallbladder contractions during the process of AC.METHODS Methylene blue(MB)with light was used to establish selective impaired ICCs gallbladder tissue.Gallbladder motility was assessed using the frequency of SW and gallbladder muscle contractility in vitro in normal control(NC),AC12h,AC24h,and AC48h groups of guinea pigs.Hematoxylin and eosin and Massonstained gallbladder tissues were scored for inflammatory changes.ICCs pathological changes alterations were estimated using immunohistochemistry and transmission electron microscopy.The alterations of c-Kit,α-SMA,cholecystokinin A receptor(CCKAR),and connexin 43(CX43)were assessed using Western blot.RESULTS Impaired ICCs muscle strips resulted in the decrease in gallbladder SW frequency and contractility.The frequency of SW and gallbladder contractility were significantly lower in the AC12h group.Compared with the NC group,the density and ultrastructure of ICCs were remarkably impaired in the AC groups,especially in the AC12h group.The protein expression levels of c-Kit were significantly decreased in the AC12h group,while CCKAR and CX43 protein expression levels were significantly decreased in the AC48h group.CONCLUSION Loss ICCs could lead to a decrease in gallbladder SW frequency and contractility.The density and ultrastructure of ICCs were clearly impaired in the early stage of AC,while CCKAR and CX43 were significantly reduced at end stage.
基金Supported by National Natural Science Foundation of China,No.81670514 and No.81702337Scientific Research Project of Shanghai Municipal Health Commission,No.202040065Natural Science Foundation of Shanghai Scientific and Technological Project of Innovative Action,No.20ZR1411900.
文摘BACKGROUND The lack of effective pharmacotherapies for nonalcoholic fatty liver disease(NAFLD)is mainly attributed to insufficient research on its pathogenesis.The pathogenesis of TM6SF2-efficient NAFLD remains unclear,resulting in a lack of therapeutic strategies for TM6SF2-deficient patients.AIM To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency.METHODS Liver samples collected from both NAFLD mouse models and human participants(80 cases)were used to evaluate the expression of TM6SF2 by using western blotting,immunohistochemistry,and quantitative polymerase chain reaction.RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2.Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD.MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency.RESULTS Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models.TM6SF2 overexpression can reduce hepatic lipid accumulation,suggesting a protective role for TM6SF2 in a high-fat diet(HFD).Downregulation of TM6SF2,simulating the TM6SF2 E167K mutation condition,increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis,accompanied by impaired fatty acid oxidation.Owing to the potential effect of TM6SF2 deficiency on lipid metabolism,the application of an acetyl-CoA carboxylase inhibitor(MK-4074)could reverse the NAFLD phenotypes caused by TM6SF2 deficiency.CONCLUSION TM6SF2 plays a protective role in the HFD condition;its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism,and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.
基金Supported by the Key Specialty Construction Project of Shanghai Pudong New Area Health Commission,No.PWZzk2022-17Shanghai East Hospital Clinical Research Project,No.DFLC2022019and the Featured Clinical Discipline Project of Shanghai Pudong District,No.PWYts2021-06.
文摘BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface barrier.Notably,these enzymes play a significant role in the development of diverse tumors.AIM To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma(CCA).METHODS We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression Omnibus.The study identified differentially expressed genes between tumor tissues and adjacent normal tissues,with a focus on PLA2G2A and PLA2G12B.Gene Set Enrichment Analysis was utilized to pinpoint associated pathways.Moreover,relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted,and their correlation with the prognosis of CCA was evaluated.RESULTS PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA,manifesting significant variations in expression levels in urine and serum between CCA patients and healthy individuals.Elevated expression of PLA2G2A was correlated with poorer overall survival in CCA patients.Additionally,the study delineated pathways and miRNAs associated with these genes.CONCLUSION Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for CCA.The increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA,and their expression levels are indicative of prognosis,underscoring their potential utility in clinical settings.
文摘The physiological function of the gastrointestinal(GI)tract is based on the slow wave generated and transmitted by the interstitial cells of Cajal.Extracellular myoelectric recording techniques are often used to record the characteristics and propagation of slow wave and analyze the models of slow wave transmission under physiological and pathological conditions to further explore the mechanism of GI dysfunction.This article reviews the application and research progress of electromyography,bioelectromagnetic technology,and high-resolution mapping in animal and clinical experiments,summarizes the clinical application of GI electrical stimulation therapy,and reviews the electrophysiological research in the biliary system.
